WO2013000895A1 - Dha and epa in the reduction of oxidative stress - Google Patents

Dha and epa in the reduction of oxidative stress Download PDF

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Publication number
WO2013000895A1
WO2013000895A1 PCT/EP2012/062326 EP2012062326W WO2013000895A1 WO 2013000895 A1 WO2013000895 A1 WO 2013000895A1 EP 2012062326 W EP2012062326 W EP 2012062326W WO 2013000895 A1 WO2013000895 A1 WO 2013000895A1
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Prior art keywords
composition
accordance
weight
dha
epa
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PCT/EP2012/062326
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French (fr)
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WO2013000895A9 (en
Inventor
Mohamed Nabil Bosco
Manuel Oliveira
Frederic Destaillats
Jalil Benyacoub
Viral BRAHMBHATT
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Nestec S.A.
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Priority to MX2013015419A priority Critical patent/MX2013015419A/en
Priority to CN201280031582.9A priority patent/CN103648494A/en
Priority to EP12730510.0A priority patent/EP2726070A1/en
Priority to AU2012277977A priority patent/AU2012277977A1/en
Priority to CA2838976A priority patent/CA2838976C/en
Priority to US14/127,606 priority patent/US20140186454A1/en
Priority to JP2014517649A priority patent/JP6378629B2/en
Priority to BR112013033438A priority patent/BR112013033438A2/en
Publication of WO2013000895A1 publication Critical patent/WO2013000895A1/en
Publication of WO2013000895A9 publication Critical patent/WO2013000895A9/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
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    • A23K—FODDER
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    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • A—HUMAN NECESSITIES
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    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention generally relates to the prevention or treatment of disorders related to oxidative stress.
  • the present invention provides a composition for use in the prevention or treatment of oxidative stress related disorders under post-operative conditions.
  • One embodiment of the present invention is a composition comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as active ingredients for use in the treatment or prevention of oxidative stress and/or related disorders.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • compositions that - when administered - allow to treat, prevent or alleviate disorders related to oxidative stress, in particular following ischemia reperfusion (IR).
  • IR ischemia reperfusion
  • the inventors provide a composition comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can successfully be used in the treatment, prevention or alleviation of oxidative stress and/or related disorders, for example induced by ischemia-reperfusion, and/or post-operative conditions related thereto. Dietary intervention with omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to be important for brain development and for the reduction of cardiovascular disease deaths.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • the inventors demonstrate that increased intake of EPA and DHA can prevent mucosal damage without having an effect on neutrophil infiltration (MPO content) , however, it reduces their activity (ROS) .
  • oxidative stress mediators CAT & SOD
  • cytokines oxidative stress mediators
  • Quantitative analytical methodologies following intestinal IR injury and after intervention with EPA and DHA were used to characterize the impact of our dietary intervention on anti-inflammatory eicosanoid generation (e.g. 17, 18-EEP and TXB3).
  • the present invention relates to a composition comprising DHA and EPA as active ingredients for use in the treatment, prevention or alleviation of oxidative stress and/or related disorders.
  • the present invention also concerns the use of DHA and EPA as active ingredients in the preparation of a composition for the treatment, prevention or alleviation of oxidative stress and/or related disorders.
  • composition of the present invention was shown to be in particularly useful if it is for use in the treatment, prevention or alleviation of oxidative stress and/or related disorders under post operative conditions.
  • oxidative stress and/or related disorders may be induced by ischemia-reperfusion .
  • Ischemia-reperfusion injury may lead to a massive generation of free oxygen radicals, which may oxidize the cellular structures. This is counter-productive for a healing process, e.g., after an operation.
  • the present invention allows treating, alleviating or preventing the negative impact of the resulting oxidative stress.
  • composition may hence be for use under hospitalized conditions for example.
  • composition was shown to be in particular effective if it contains EPA and DHA.
  • EPA and DHA may be obtained from any source. They may be synthesized or purified from natural compounds. Preferably, they are provided as a natural composition or as an extract thereof.
  • DHA and EPA may be provided from a lipid source comprising marine oils, such as fish oil or from microorganisms.
  • the fish oil or the whole lipid source may be provided in an encapsulated form.
  • the composition may comprise other lipids.
  • the lipid source may comprise cocoa butter, soybean oil, fish oil and/or sunflower oil.
  • the lipid source may be adjusted to meet the nutritional needs of the subject to be treated.
  • the lipid source may correspond to about 7-13%, for example about 10%, of the caloric content of the composition.
  • the essential fatty acids, linoleic acid and alpha-linolenic acid may correspond to about 3-5.5%, for example about 4.4%, and about 0.1-0.5%, for example about 0.3%, respectively, of the total caloric content of the composition.
  • EPA and DHA may be contained in the composition in an amount corresponding to about 0.2-0.4%, for example about 0.3%, and about 0.1-0.3%, for example about 0.2%, respectively of the total energy intake.
  • such a lipid source may comprise about 5-10 weight-% cocoa butter, about 45-55 weight-% soybean oil, about 15-25 weight-% fish oil and about 20-25 weight-% sunflower oil .
  • the lipid source may comprise about 7 weight % cocoa butter, about 50 weight-% soybean oil, about 20 weight-% fish oil and about 23 weight-% sunflower oil.
  • such a lipid source comprises a mixture of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids.
  • the amounts of these fatty acids may be adjusted based on the needs of the subject to be treated.
  • the lipid source may comprise about 18-22 weight- % saturated fatty acids, about 20-25 weight-% monounsaturated fatty acids and about 50-55 weight-% polyunsaturated fatty acids .
  • Oxidative damage is often mediated by reactive oxygen species.
  • Such reactive oxygen species may be free radicals, for example .
  • the oxidative stress related disorder may be linked to the presence of free radicals in a body such as ⁇ 0 2 ⁇ , the superoxide anion; H 2 O 2 , hydrogen peroxide; ⁇ , the hydroxyl radical; ROOH, organic hydroperoxide; RO, alkoxy radicals; ROO » , peroxy radicals; HOC1, hypochlorous acid; OONO ⁇ , peroxynitrite ; and/or NO .
  • free radicals in a body such as ⁇ 0 2 ⁇ , the superoxide anion; H 2 O 2 , hydrogen peroxide; ⁇ , the hydroxyl radical; ROOH, organic hydroperoxide; RO, alkoxy radicals; ROO » , peroxy radicals; HOC1, hypochlorous acid; OONO ⁇ , peroxynitrite ; and/or NO .
  • composition of the present invention reduces the risk for such direct or indirect damage of organs and may consequently be used in the treatment or prevention of oxidative damage to intestine, liver, lung, heart, kidney, and/or skin.
  • the oxidative stress related disorder may be any such disorder .
  • the oxidative stress related disorder may be selected from the group consisting of an inflammatory response to oxidative stress, retinal degeneration, mitohormesis , atherosclerosis, amyotrophic lateral sclerosis (ALS) , multiple sclerosis (MS), Friedreich's ataxia, tardive dyskynesia, brain injuries such as ischemia, skin photoaging, reperfusion injury or stroke, myocardial infarction, hypertension, heart failure, epilepsy, hyperhomocysteinemia, physiological senescence, sepsis, stress following organ transplantation or combinations thereof .
  • ALS amyotrophic lateral sclerosis
  • MS multiple sclerosis
  • Friedreich's ataxia Huntive dyskynesia
  • brain injuries such as ischemia, skin photoaging, reperfusion injury or stroke, myocardial infarction, hypertension, heart failure, epilepsy, hyperhomocysteinemia, physiological senescence, sepsis, stress following organ transplantation or combinations thereof .
  • composition of the present invention can very successfully be used to limit intestinal damages following ischemia-reperfusion (IR), e.g., in the splanchnic area. Consequently, in particular visceral organs may be protected by the composition of the present invention.
  • IR ischemia-reperfusion
  • composition of the present invention follows a dose-response curve.
  • compositions are administered in an amount sufficient to at least partially cure or arrest the symptoms of the disease and its complications.
  • An amount adequate to accomplish this is defined as "a therapeutically effective dose”. Amounts effective for this purpose will depend on a number of factors known to those of skill in the art such as the severity of the disease and the weight and general state of the patient.
  • compositions according to the invention are administered to a patient susceptible to or otherwise at risk of a particular disease in an amount that is sufficient to at least partially reduce the risk of developing a disease.
  • a prophylactically effective dose Such an amount is defined to be "a prophylactically effective dose”.
  • the compositions of the present invention may be administered in a a therapeutically effective dose or a prophylactically effective dose. Skilled artisans will be able to determine these dosages based on the information provided herein and the state of the patient. For example, the composition may be to de administered in an amount corresponding to a combined daily dosage of EPA and DHA are of at least 40_0 mg.
  • EPA and DHA may be provided in any ratio, for example in a weight ratio in the range of 10:1 to 1:10, for example 7:1 to 1:1, e.g. about 5:1 to 1:1.
  • EPA and DHA are comprised in the composition in a weight ratio in the range of about 2:1 to 1:1. Very good results were obtained with a weight ratio of EPA and DHA in the range of about 3:2.
  • the compositions may be to be administered in amounts corresponding to a combined daily intake of EPA and DHA of about 2-5 g, for example, 3-4 g.
  • compositions of the present invention consecutively over a period of several days.
  • the administration may begin for example 7 days, 3 days, 2 days or 1 day before the operation as preventive measure.
  • the administration may begin 3 to 7 days before an intervention.
  • the administration may also be started immediately after the operation and/or ischemia-reperfusion .
  • composition may be to be administered daily over a period of at least 3 days, for example at least a week or at least two weeks .
  • composition of the present invention may be to be administered to any patient.
  • the patient may be a human or animal patient.
  • the animal may be a companion animal such as a dog or a cat.
  • compositions may be to be administered topically, orally, enterally or parenterally.
  • the compositions will be administered orally with the normal food intake. Should the normal food intake be not possible, the composition may be to be administered enterally, e.g., via tube feeding, or in severe cases, where enteral administration is not possible or not advised parenterally . In cases of parenteral administration the composition usually does not contain a carbohydrate source, but carbohydrates may be administered separately, via a glucose drip, for example.
  • the composition may be administered as a food product or as a drinkable composition.
  • the composition may be selected from the group consisting of a food product, a pet food product, a nutraceutical , a drink, a food supplement, a powdered nutritional formula to be reconstituted in milk or water, or a medicament .
  • mice At the end of the third week under control or NRC supplemented diets, animals underwent either a sham procedure or an I/R surgical protocol, which consists of a 30 min ischemic period followed by a 3h reperfusion period (as described in Yoshida N. et al . Mol Med Report, 2011 4:81-86). At the end of the reperfusion period, animals were sacrificed then sera and organs were collected.
  • Maintenance AIN-93M diet contains 10% of total energy provided as fat.
  • the essential fatty acids, linoleic acid and alpha- linolenic acid provide ⁇ 4.4% and 0.3% of the total energy intake respectively.
  • NRC interventional diet we kept these values as close as possible to control with a specific blend described below.
  • EPA and DHA while absent in the control diet are provided in the supplemented diet in amounts that are close to fish oil, ⁇ 0.3% and 0.2% of total energy intake, respectively.
  • Table la and b give the lipid blend description and nature of fatty acid contained.

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Abstract

The present invention generally relates to the prevention or treatment of disorders related to oxidative stress. For example, the present invention provides a composition for use in the prevention or treatment of oxidative stress related disorders under post-operative conditions. One embodiment of the present invention is a composition comprising DHA and EPA as active ingredients for use in the treatment or prevention of oxidative stress and/or related disorders.

Description

DHA and EPA in the reduction of oxidative stress
The present invention generally relates to the prevention or treatment of disorders related to oxidative stress. For example, the present invention provides a composition for use in the prevention or treatment of oxidative stress related disorders under post-operative conditions. One embodiment of the present invention is a composition comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as active ingredients for use in the treatment or prevention of oxidative stress and/or related disorders.
Intestinal damages as a result of ischemia and subsequent reperfusion plays a key role in complications of various adult surgical procedures and neonatal clinical conditions i.e. solid organ transplantation, septic shock and necrotizing enterocolitis (NEC) (reviewed in Nowicki PT et al. Clin. Perinatol., 1994 21:219-234, Carden DL et al . J. Pathol., 2009 190: 255-266 and Cerqueira NF et al . Acta Cir. Bras., 2009 24 : 290-295) . Numerous lines of evidence suggest that the generation of reactive oxygen species (ROS) and ROS-mediated damages play a central role in intestinal IR injuries.
Apart from an increase in ROS production intestinal IR leads to ROS-dependent and independent activation of and complex downstream cascades which are not well understood. The outcome of this activation is an increased expression of neutrophil adhesion molecules, inflammatory cytokines and lipid proinflammatory metabolites derived from arachidonic acid (i.e. eicosanoids) . This eventually leads to mucosal injury causing increased barrier permeability which is partly responsible for distant organ damages and surgical complications. In order to reduce oxidative stress related disorders following ischemia reperfusion, for example, authors suggest a treatment with ant i-oxidant s such as vitamin C (Lloberas et al., FASEB J. April 23, 2002, page 908-910). However, vitamin C is quickly secreted from the body and may not be efficiently active unless used in repetitive and high amounts with possible side effects.
Consequently, there is a need in the art for alternative compositions that - when administered - allow to treat, prevent or alleviate disorders related to oxidative stress, in particular following ischemia reperfusion (IR).
The present inventors have addressed this need.
Hence, it was the objective of the present invention to provide the art with a composition that can be used to treat or prevent disorders related to oxidative stress, for example after ischemia reperfusion, that it easy and safe to administer, is natural and has no unwanted side effects.
The present inventors were surprised to see that they could achieve this objective by the subject matter of the independent claim. The dependant claims further develop the idea of the present invention.
The inventors provide a composition comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can successfully be used in the treatment, prevention or alleviation of oxidative stress and/or related disorders, for example induced by ischemia-reperfusion, and/or post-operative conditions related thereto. Dietary intervention with omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to be important for brain development and for the reduction of cardiovascular disease deaths. The current worldwide intake of EPA and DHA varies greatly and correlates well with burden of diseases that can potentially be modified by increasing EPA and DHA intake (review in Hibbeln JR et al . Am. J. Clin. Nutr., 2006 83: 1483-1493) The inventors report the effects of a dietary intervention based on a lipid blend allowing an efficient increase of systemic and intestinal EPA and DHA content after 3 weeks and conferring a protection against mucosal damages following intestinal IR injury induced by temporary occlusion of mesenteric artery.
The inventors demonstrate that increased intake of EPA and DHA can prevent mucosal damage without having an effect on neutrophil infiltration (MPO content) , however, it reduces their activity (ROS) .
In order to investigate the underlying mechanisms, the inventors measured changes in oxidative stress mediators (CAT & SOD) and cytokines. Quantitative analytical methodologies following intestinal IR injury and after intervention with EPA and DHA were used to characterize the impact of our dietary intervention on anti-inflammatory eicosanoid generation (e.g. 17, 18-EEP and TXB3).
The results of this study show beneficial effects on mucosal damages via a reduction in oxidative stress.
Consequently, the present invention relates to a composition comprising DHA and EPA as active ingredients for use in the treatment, prevention or alleviation of oxidative stress and/or related disorders.
The present invention also concerns the use of DHA and EPA as active ingredients in the preparation of a composition for the treatment, prevention or alleviation of oxidative stress and/or related disorders.
The composition of the present invention was shown to be in particularly useful if it is for use in the treatment, prevention or alleviation of oxidative stress and/or related disorders under post operative conditions.
For example the oxidative stress and/or related disorders may be induced by ischemia-reperfusion .
Ischemia-reperfusion injury may lead to a massive generation of free oxygen radicals, which may oxidize the cellular structures. This is counter-productive for a healing process, e.g., after an operation. The present invention allows treating, alleviating or preventing the negative impact of the resulting oxidative stress.
The composition may hence be for use under hospitalized conditions for example.
The composition was shown to be in particular effective if it contains EPA and DHA.
EPA and DHA may be obtained from any source. They may be synthesized or purified from natural compounds. Preferably, they are provided as a natural composition or as an extract thereof. For example DHA and EPA may be provided from a lipid source comprising marine oils, such as fish oil or from microorganisms.
As fish oils often have a taste and/or smell that may be perceived as unpleasant, the fish oil or the whole lipid source may be provided in an encapsulated form.
Compounds that are known to prevent the generation of unwanted off-tastes or odors, such as lecithin or the juice of citrus fruits, for example, may be added.
The composition may comprise other lipids. For example, the lipid source may comprise cocoa butter, soybean oil, fish oil and/or sunflower oil.
For example, the lipid source may be adjusted to meet the nutritional needs of the subject to be treated. For example, the lipid source may correspond to about 7-13%, for example about 10%, of the caloric content of the composition.
The essential fatty acids, linoleic acid and alpha-linolenic acid, may correspond to about 3-5.5%, for example about 4.4%, and about 0.1-0.5%, for example about 0.3%, respectively, of the total caloric content of the composition. In addition EPA and DHA may be contained in the composition in an amount corresponding to about 0.2-0.4%, for example about 0.3%, and about 0.1-0.3%, for example about 0.2%, respectively of the total energy intake.
This may be achieved by several different oil mixtures, which all can be used and which may be selected according to taste or other preferences.
For example such a lipid source may comprise about 5-10 weight-% cocoa butter, about 45-55 weight-% soybean oil, about 15-25 weight-% fish oil and about 20-25 weight-% sunflower oil .
The lipid source may comprise about 7 weight % cocoa butter, about 50 weight-% soybean oil, about 20 weight-% fish oil and about 23 weight-% sunflower oil.
Typically, such a lipid source comprises a mixture of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids.
The amounts of these fatty acids may be adjusted based on the needs of the subject to be treated.
For example, the lipid source may comprise about 18-22 weight- % saturated fatty acids, about 20-25 weight-% monounsaturated fatty acids and about 50-55 weight-% polyunsaturated fatty acids . Oxidative damage is often mediated by reactive oxygen species. Such reactive oxygen species may be free radicals, for example .
Consequently, the oxidative stress related disorder may be linked to the presence of free radicals in a body such as ·02~, the superoxide anion; H2O2, hydrogen peroxide; ·ΟΗ, the hydroxyl radical; ROOH, organic hydroperoxide; RO, alkoxy radicals; ROO», peroxy radicals; HOC1, hypochlorous acid; OONO~ , peroxynitrite ; and/or NO .
Many organs can be either directly or indirectly damaged by oxidative stress. Indirect damage is often seen in remote organs following reperfusion. Such indirect damage is problematic as it can lead, e.g., to a multiple organ disturbance syndrome following intestine ischemia reperfusion. Oftentimes the lung may be affected by indirect damage.
The composition of the present invention reduces the risk for such direct or indirect damage of organs and may consequently be used in the treatment or prevention of oxidative damage to intestine, liver, lung, heart, kidney, and/or skin.
The oxidative stress related disorder may be any such disorder .
For example, the oxidative stress related disorder may be selected from the group consisting of an inflammatory response to oxidative stress, retinal degeneration, mitohormesis , atherosclerosis, amyotrophic lateral sclerosis (ALS) , multiple sclerosis (MS), Friedreich's ataxia, tardive dyskynesia, brain injuries such as ischemia, skin photoaging, reperfusion injury or stroke, myocardial infarction, hypertension, heart failure, epilepsy, hyperhomocysteinemia, physiological senescence, sepsis, stress following organ transplantation or combinations thereof .
The inventors have demonstrated experimentally by means of example using a rodent model that the composition of the present invention can very successfully be used to limit intestinal damages following ischemia-reperfusion (IR), e.g., in the splanchnic area. Consequently, in particular visceral organs may be protected by the composition of the present invention.
The effectiveness of the composition of the present invention follows a dose-response curve.
In therapeutic applications, compositions are administered in an amount sufficient to at least partially cure or arrest the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as "a therapeutically effective dose". Amounts effective for this purpose will depend on a number of factors known to those of skill in the art such as the severity of the disease and the weight and general state of the patient.
In prophylactic applications, compositions according to the invention are administered to a patient susceptible to or otherwise at risk of a particular disease in an amount that is sufficient to at least partially reduce the risk of developing a disease. Such an amount is defined to be "a prophylactically effective dose". Again, the precise amounts depend on a number of patient specific factors such as the patient's state of health and weight. The compositions of the present invention may be administered in a a therapeutically effective dose or a prophylactically effective dose. Skilled artisans will be able to determine these dosages based on the information provided herein and the state of the patient. For example, the composition may be to de administered in an amount corresponding to a combined daily dosage of EPA and DHA are of at least 40_0 mg.
EPA and DHA may be provided in any ratio, for example in a weight ratio in the range of 10:1 to 1:10, for example 7:1 to 1:1, e.g. about 5:1 to 1:1.
Preferably, EPA and DHA are comprised in the composition in a weight ratio in the range of about 2:1 to 1:1. Very good results were obtained with a weight ratio of EPA and DHA in the range of about 3:2. In clinical settings the compositions may be to be administered in amounts corresponding to a combined daily intake of EPA and DHA of about 2-5 g, for example, 3-4 g.
For best results it is advisable to administer the compositions of the present invention consecutively over a period of several days.
If an operation is planned, and in particular if an ischemia- reperfusion is foreseen, the administration may begin for example 7 days, 3 days, 2 days or 1 day before the operation as preventive measure.
For example, the administration may begin 3 to 7 days before an intervention.
The administration may also be started immediately after the operation and/or ischemia-reperfusion .
The composition may be to be administered daily over a period of at least 3 days, for example at least a week or at least two weeks .
The composition of the present invention may be to be administered to any patient. The patient may be a human or animal patient. The animal may be a companion animal such as a dog or a cat.
The compositions may be to be administered topically, orally, enterally or parenterally.
Typically, the compositions will be administered orally with the normal food intake. Should the normal food intake be not possible, the composition may be to be administered enterally, e.g., via tube feeding, or in severe cases, where enteral administration is not possible or not advised parenterally . In cases of parenteral administration the composition usually does not contain a carbohydrate source, but carbohydrates may be administered separately, via a glucose drip, for example.
Typically, however, the composition may be administered as a food product or as a drinkable composition. As such, the composition may be selected from the group consisting of a food product, a pet food product, a nutraceutical , a drink, a food supplement, a powdered nutritional formula to be reconstituted in milk or water, or a medicament . Those skilled in the art will understand that they can freely combine all features of the present invention described herein, without departing from the scope of the invention as disclosed. In particular, features described for the uses of the present invention may be applied to the composition of the present invention and vice versa.
Further advantages and features of the present invention are apparent from the following Examples.
Examples :
8 week old male Sprague-Dawley rats (Charles-River - France) were used. Animals were received two weeks prior to dietary intervention for acclimatation in our animal facility. All animals were kept under 12 h light/dark cycles at constant room temperature in specific pathogen-free conditions. They had free access to a commonly used basal diet (AIN-93M) and tap water.
After two weeks, rats were randomly assigned to one of three different experimental groups (n=8 per group) i.e. (i) Sham group- this group was provided control diet for 3 weeks and underwent a sham surgical procedure; (ii) I/R group- this group was provided control diet for 3 weeks followed by I/R surgical protocol and (iii) I/R+ NRC lipid blend group- this group was provided diet supplemented with a lipid blend (described below) for 3 weeks and underwent I/R surgical protocol at the end of dietary intervention.
At the end of the third week under control or NRC supplemented diets, animals underwent either a sham procedure or an I/R surgical protocol, which consists of a 30 min ischemic period followed by a 3h reperfusion period (as described in Yoshida N. et al . Mol Med Report, 2011 4:81-86). At the end of the reperfusion period, animals were sacrificed then sera and organs were collected.
Maintenance AIN-93M diet contains 10% of total energy provided as fat. The essential fatty acids, linoleic acid and alpha- linolenic acid provide ~ 4.4% and 0.3% of the total energy intake respectively. In the NRC interventional diet, we kept these values as close as possible to control with a specific blend described below. In addition EPA and DHA while absent in the control diet are provided in the supplemented diet in amounts that are close to fish oil, ~ 0.3% and 0.2% of total energy intake, respectively.
Total small intestine protein, superoxide dismutase, catalase, nitrate / nitrite, MPO content or activities were measured with commercially available kits (from Roche, Sigma or Cayman) . EPA and DHA incorporation were measured with standard HPLC methods and adequate commercially available standards. Eicosanoids were quantified by HPLC-MS/MS with adequate commercially available standards as described in Pouteau E. et al. Nutr Metab, 2010 7:8.
All the data presented herein are expressed as mean ± SEM. Comparison of the three groups was made using Student's t-test for unpaired data when appropriate. Differences were considered statistically significant for P value <0.05.
Results
Table la and b give the lipid blend description and nature of fatty acid contained.
a .
Figure imgf000014_0001
Table 2 summarizes biochemical measured made with animals (n=8/group) .
Figure imgf000015_0001
Non-esterified 95.2+44.8 69.8+27.1 492.3 +240.6 * EPA
(ng/mg tissue)
Non-esterified 73.2+28.3 69.6+23.3 152.2 +69.6 * DHA (ng/mg
tissue)
17, 18-EEP 0.3+0.2 0.2+0.1 3.1 +2.1 * (ng/mg tissue)
TXB3 0.14+0.08 0.14+0.03 0.50 +0.37 *
(ng/mg tissue)
Conclusions
Our study demonstrate that our particular lipid blend enriched with omega-3 fatty acids can (e.g., when incorporated in a food matrix) limit e.g. intestinal oxidative stress related damages following ischemia-reperfusion (IR) in the splanchnic area. Interestingly, NRC lipid blend fed animals display a higher expression of enzymes of the oxidative stress machinery and lipidomic analyses of intestinal tissue clearly show global increase of antiinflammatory lipid metabolites . The present results show for the first time how a dietary intervention can modulate eicosanoid formation and limit events associated to IR damages.

Claims

Claims
1. Composition comprising DHA and EPA as active ingredients for use in the treatment, prevention or alleviation of oxidative stress and/or related disorders induced by ischemia-reperfusion .
Composition for use in accordance with claim 1 comprising EPA and DHA in a weight ratio in the range of about 2:1 to 1:1, preferably about 3:2.
Composition for use in accordance with one of the preceding claims wherein DHA and EPA are provided from a lipid source comprising marine oils, such as fish oil.
Composition for use in accordance with claim 3, wherein the lipid source comprises cocoa butter, soybean oil, fish oil and sunflower oil.
Composition for use in accordance with claim 4, wherein the lipid source comprises about 5-10 weight-% cocoa butter, about 45-55 weight-% soybean oil, about 15-25 weight-% fish oil and about 20-25 weight-% sunflower oil.
Composition for use in accordance with claim 3, wherein the lipid source comprises about 18-22 weight-% saturated fatty acids, about 20-25 weight-% monounsaturated fatty acids and about 50-55 weight-% polyunsaturated fatty acids .
Composition for use in accordance with one of the preceding claims, wherein the oxidative stress related disorder is linked to the presence of free radicals in a body such as ·02~, the superoxide anion; H2O2, hydrogen peroxide; ·ΟΗ, the hydroxyl radical; ROOH, organic hydroperoxide; RO, alkoxy radicals; ROO, peroxy radicals; H0C1, hypochlorous acid; 00N0~, peroxynitrite ; and/or NO .
8. Composition for use in accordance with one of the preceding claims in the treatment or prevention of oxidative damage to intestine, liver, lung, heart, kidney, and/or skin.
9. Composition for use in accordance with one of the preceding claims, wherein the oxidative stress related disorder is selected from the group consisting of an inflammatory response to oxidative stress, retinal degeneration, mitohormesis , atherosclerosis, amyotrophic lateral sclerosis (ALS) , multiple sclerosis (MS) , Friedreich's ataxia, tardive dyskynesia, brain injuries such as ischemia, skin photoaging, reperfusion injury or stroke, myocardial infarction, hypertension, heart failure, epilepsy, hyperhomocysteinemia, physiological senescence, sepsis, stress following organ transplantation or combinations thereof.
10. Composition for use in accordance with one of the preceding claims to limit intestinal damages following ischemia-reperfusion (IR), e.g., in the splanchnic area.
11. Composition for use in accordance with one of the preceding claims, wherein EPA and DHA are provided in a daily dose of at least 40_0 mg.
12. Composition for use in accordance with one of the preceding claims, wherein the composition is to be administered daily over a period of at least 3 days, for example at least a week or at least two weeks.
13. Composition for use in accordance with one of the preceding claims, to be administered to human or pets, for example companion animals such as dogs or cats.
14. Composition for use in accordance with one of the preceding claims to be administered topically, orally, enterally or parenterally.
15. Composition for use in accordance with one of the preceding claims wherein the composition is selected from the group consisting of a food product, a pet food product, a nutraceutical , a drink, a food supplement, a powdered nutritional formula to be reconstituted in milk or water, or a medicament.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050171200A1 (en) * 2002-03-05 2005-08-04 Philip Calder Use of EPA and DHA in secondary prevention
US20070020340A1 (en) * 2005-07-25 2007-01-25 David Rubin Fish oil products for reducing cholesterol, low density lipoprotein, and hypertension
US20100056484A1 (en) * 2008-08-26 2010-03-04 Scott Farese Dietary supplemental composition effective for enhancing cognitive performance, elevating mood and reducing oxidative stress

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8819110D0 (en) * 1988-08-11 1988-09-14 Norsk Hydro As Antihypertensive drug & method for production
TR199900786T2 (en) * 1996-10-11 1999-07-21 Scotia Holdings Plc Pharmaceutical compositions containing Eykoza penta enoic acid and/or stearidonic acid.
GB0111282D0 (en) * 2001-05-09 2001-06-27 Laxdale Ltd Potentiation of therapeutic effects of fatty acids
US20040235163A1 (en) * 2001-08-22 2004-11-25 Mitsuhiro Yokota Myocardial cell apoptosis inhibitors
US6984636B2 (en) * 2002-08-12 2006-01-10 Medical Research Council Mitochondrially targeted antioxidants
US20060009486A1 (en) * 2004-07-07 2006-01-12 Gm Pharmaceuticals Inc. Composition and method for treatment and prevention of coronary artery disease
CA2574366A1 (en) * 2004-07-19 2006-01-26 Thia Medica As Composition comprising plant and/or fish oils and compounds comprising non-oxidizable fatty acid entities
KR20080005563A (en) * 2005-04-21 2008-01-14 글렌 에이. 골드스타인 N-acetylcysteine amide(nac amide) for treatment of oxidative stress associated with infertility
WO2007115934A1 (en) * 2006-04-12 2007-10-18 Unilever Plc Oral composition with an antiageing effect on the skin
US20080015218A1 (en) * 2006-07-12 2008-01-17 Novus International Inc. Antioxidant combinations for use in ruminant feed rations having a fat source
WO2008036353A2 (en) * 2006-09-19 2008-03-27 The Trustees Of Columbia University In The City Of New York Omega-3 diglyceride emulsions
JP5128828B2 (en) * 2007-02-16 2013-01-23 月桂冠株式会社 Anti-inflammatory and antioxidant
WO2010074940A1 (en) * 2008-12-23 2010-07-01 Alcon Research, Ltd. Compositions and nutritional supplements for improving ocular health and reducing ocular inflammatory response
US7928067B2 (en) * 2009-05-14 2011-04-19 Ischemix Llc Compositions and methods for treating ischemia and ischemia-reperfusion injury
US8426368B2 (en) * 2010-03-25 2013-04-23 The University Of Kentucky Research Foundation Method of ameliorating oxidative stress and supplementing the diet
EP2425833A1 (en) * 2010-09-03 2012-03-07 Fresenius Kabi Deutschland GmbH Intravenous application of fish oils / DHA + EPA before or at the beginning of chemotherapy

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050171200A1 (en) * 2002-03-05 2005-08-04 Philip Calder Use of EPA and DHA in secondary prevention
US20070020340A1 (en) * 2005-07-25 2007-01-25 David Rubin Fish oil products for reducing cholesterol, low density lipoprotein, and hypertension
US20100056484A1 (en) * 2008-08-26 2010-03-04 Scott Farese Dietary supplemental composition effective for enhancing cognitive performance, elevating mood and reducing oxidative stress

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
CARDEN DL ET AL., J. PATHOL., vol. 190, 2009, pages 255 - 266
CERQUEIRA NF ET AL., ACTA CIR. BRAS., vol. 24, 2009, pages 290 - 295
HIBBELN JR ET AL., AM. J. CLIN. NUTR., vol. 83, 2006, pages 1483 - 1493
KOTHNY W ET AL: "Short term effects of omega-3 fatty acids on the radial artery of patients with coronary artery disease.", ATHEROSCLEROSIS SEP 1998 LNKD- PUBMED:9733230, vol. 140, no. 1, September 1998 (1998-09-01), pages 181 - 186, XP002658151, ISSN: 0021-9150 *
LLOBERAS ET AL., FASEB J., 23 April 2002 (2002-04-23), pages 908 - 910
MAYER KONSTANTIN ET AL: "Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis.", AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 15 MAY 2003 LNKD- PUBMED:12615625, vol. 167, no. 10, 15 May 2003 (2003-05-15), pages 1321 - 1328, XP002658150, ISSN: 1073-449X *
NOWICKI PT ET AL., CLIN. PERINATOL., vol. 21, 1994, pages 219 - 234
OZ HELIEH S ET AL: "Nutrition intervention: a strategy against systemic inflammatory syndrome", JPEN. JOURNAL OF PARENTERAL AND ENTERAL NUTRITION, July 2009 (2009-07-01), pages 1 - 20, XP002658152, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063840/?tool=pubmed> [retrieved on 20110905] *
POUTEAU E. ET AL., NUTR METAB, vol. 7, 2010, pages 8
YOSHIDA N. ET AL., MOL MED REPORT, vol. 4, 2011, pages 81 - 86

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